Evidence map›Paper›PMID 39143171›Full record

ArticleScientific reports2024

The significance of upper glycolytic components in regulating retinal pigment epithelial cellular behavior.

Armaan Naghdi, Nicole Oska, Thangal Yumnamcha, Shaimaa Eltanani, Mohamed Shawky, Rao Me, Ahmed S Ibrahim

Abstract read
In one paragraph

Article in Scientific reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Armaan NaghdiDepartment of Ophthalmology, Visual, and Anatomical Sciences, School of Medicine, Wayne State University, 540 East Canfield, Gordon Scott Hall (Room 7133), Detroit, MI, 48201, USA.
Nicole OskaDepartment of Ophthalmology, Visual, and Anatomical Sciences, School of Medicine, Wayne State University, 540 East Canfield, Gordon Scott Hall (Room 7133), Detroit, MI, 48201, USA.
Thangal YumnamchaDepartment of Ophthalmology, Visual, and Anatomical Sciences, School of Medicine, Wayne State University, 540 East Canfield, Gordon Scott Hall (Room 7133), Detroit, MI, 48201, USA.
Shaimaa EltananiDepartment of Ophthalmology, Visual, and Anatomical Sciences, School of Medicine, Wayne State University, 540 East Canfield, Gordon Scott Hall (Room 7133), Detroit, MI, 48201, USA.
Mohamed ShawkyDepartment of Ophthalmology, Visual, and Anatomical Sciences, School of Medicine, Wayne State University, 540 East Canfield, Gordon Scott Hall (Room 7133), Detroit, MI, 48201, USA.
Rao MeDepartment of Ophthalmology, Visual, and Anatomical Sciences, School of Medicine, Wayne State University, 540 East Canfield, Gordon Scott Hall (Room 7133), Detroit, MI, 48201, USA.
Ahmed S IbrahimDepartment of Ophthalmology, Visual, and Anatomical Sciences, School of Medicine, Wayne State University, 540 East Canfield, Gordon Scott Hall (Room 7133), Detroit, MI, 48201, USA. ahmed.ibrahim@wayne.edu.

Funding

The Warburg Effect and Diabetic RetinopathyR01EY034964 · NEI · WAYNE STATE UNIVERSITY · PI Ahmed S Ibrahim · 2023 to 2026
$1.5M
NEI NIH HHS R01 EY034964
6 · The paper itself

Abstract

Cell adhesion to the extracellular matrix and its natural outcome of cell spreading, along with the maintenance of barrier activity, are essential behaviors of epithelial cells, including retinal pigment epithelium (RPE). Disruptions in these characteristics can result in severe vision-threatening diseases such as diabetic macular edema and age-related macular degeneration. However, the precise mechanisms underlying how RPE cells regulate their barrier integrity and cell spreading are not fully understood. This study aims to elucidate the relative importance of upper glycolytic components in governing these cellular behaviors of RPE cells. Electric Cell-Substrate Impedance Sensing (ECIS) technology was utilized to assess in real-time the effects of targeting various upper glycolytic enzymes on RPE barrier function and cell spreading by measuring cell resistance and capacitance, respectively. Specific inhibitors used included WZB117 for Glut1 inhibition, Lonidamine for Hexokinase inhibition, PFK158 for PFKFB3/PFK axis inhibition, and TDZD-8 for Aldolase inhibition. Additionally, the viability of RPE cells was evaluated using a lactate dehydrogenase (LDH) cytotoxicity assay. The most significant decrease in electrical resistance and increase in capacitance of RPE cells were observed due to dose-dependent inhibition of Glut1 using WZB117, as well as Aldolase inhibition with TDZD-8. LDH level analysis at 24-72 h post-treatment with WZB117 (1 and 10 μM) or TDZD-8 (1 μM) showed no significant difference compared to the control, indicating that the disruption of RPE functionality was not attributed to cell death. Lastly, inhibition of other upper glycolytic components, including PFKFB3/PFK with PFK158 or Hexokinase with Lonidamine, did not significantly affect RPE cell behavior. This study provides insights into the varied roles of upper glycolytic components in regulating the functionality of RPE cells. Specifically, it highlights the critical roles of Glut1 and Aldolase in preserving barrier integrity and promoting RPE cell adhesion and spreading. Such understanding will guide the development of safe interventions to treat RPE cell dysfunction in various retinal disorders.

Indexed as

Cell AdhesionElectric ImpedanceGlycolysisRetinal Pigment EpitheliumCell LineCell SurvivalEnzyme InhibitorsExtracellular MatrixFructose-Bisphosphate AldolaseGlucose Transporter Type 1HumansLactate DehydrogenasesPhosphofructokinasesEnzyme InhibitorsFructose-Bisphosphate AldolaseGlucose Transporter Type 1Lactate DehydrogenasesPhosphofructokinasesSLC2A1 protein, humanAge-related macular degeneration (AMD)Barrier integrityCapacitanceCell adhesionCell spreadingElectric cell-substrate impedance sensing (ECIS)GlycolysisResistance

Identifiers

PMID39143171
PMCPMC11324787

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.